Comparative dosimetry of copper-64 and yttrium-90-labeled somatostatin analogs in a tumor-bearing rat model

Y-90-DOTA -tyrosine(3)-octreotide (Y-90-DOTA-Y3-OC) is currently being eval uated as a radiotherapy agent for trials in patients with somatostatin-rece ptor positive cancer. In this study, we compared the estimated absorbed dos es to human organs, as well as to a CA20948 rat tumor, of Y-90- and Cu-64-l abeled DOTA-Y3-OC and DOTA-Y3-octreotate (DOTA-Y3-TATE). Assuming that the radiopharmaceutical biodistributions are the same in rodents and humans, hu man absorbed dose estimates were obtained from rat biodistribution data. Th e absorbed doses of Y-90-DOTA-Y3-TATE were determined from the biodistribut ion of the Y-88-labeled peptide, with and without co-injection of a therape utic amount of the Y-90-labeled peptide. Additionally, the absorbed doses o f Y-90-DOTA-Y3-TATE were determined from data using two different biodistri bution endpoints, 48 h and 168 h. Human absorbed dose estimates were calcul ated using MIRD methodology assuming that rats and humans have the same bio distribution. The biodistribution of the radiolabeled somatostatin analogs was dependent on the peptide and the radiometal. For 90Y-DOTA-Y3-TATE, the tumor dose was dependent on both the administration of therapeutic Y-90-pep tide and the biodistribution endpoint. Our data suggested that, for both ra dionuclides, the TATE derivatives imparted a higher absorbed dose to the tu mor than the OC analogs. Y-90-DOTA-Y3-OC and Cu-64-DOTA-Y3-OC were comparab le with respect to their tumor-to-normal tissue dose ratios, while Y-90-DOT A-Y3-TATE appeared to have distinct advantages over Cu-64-DOTA-Y3-TATE.